Our previous studies, as well as studies conducted by others, on barbiturate and ethanol have indicated that prenatal exposure to sedative hypnotics induces long-lasting behavioral, neurochemical and metabolic changes. Some preliminary studies seem to indicate that prenatal exposure to barbiturate induced neuronal loss in the offspring. We plan to use different genetic strains of mice to establish an animal model for the long-term effects of early barbiturate consumption of the morphological retardation of the central nervous system. Pregnant females will receive phenobarbital during different periods in pregnancy and the CNS of the offspring will be studied in adulthood. Areal measurements and cell counts will be taken in different regions. Golgi and electron microscope techniques will be applied to study the possible consequences of prenatal barbiturate exposure on the cell structure, particularly on the synapses. Autoradiography will be used in different periods for the study of the effect on neuronal proliferation, migration, the extent of recovery and the sensitive periods. We shall study the recovery of structure as a function of the stage in development in which the damage occurred. The effect of the genotype on sensitivity and recovery will also be evaluated. Finally, the morphological results thus obtained will be correlated with the behavioral results obtained in our other studies in structure function relationships. To date, there is no comprehensive study designed to study the possible neuromorphological retardation which may result from prenatal barbiturate consumption, despite the widespread use of drugs during pregnancy. The knowledge that will be acquired will be important from the standpoint of public health; in addition we shall provide basic information on structure function relationships in the CNS.